Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

doi:10.1183/09031936.00136312

Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

Pediatric and Adolescent Medicine

Research output: Contribution to journal › Article › peer-review

199 Scopus citations

Abstract

The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

Original language	English (US)
Pages (from-to)	169-179
Number of pages	11
Journal	European Respiratory Journal
Volume	42
Issue number	1
DOIs	https://doi.org/10.1183/09031936.00136312
State	Published - Jul 1 2013

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1183/09031936.00136312

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title = "Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis",

abstract = "The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.",

author = "{Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB} and Migliori, {Giovanni Battista} and Giovanni Sotgiu and Gandhi, {Neel R.} and Dennis Falzon and Kathryn DeRiemer and Rosella Centis and Hollm-Delgado, {Maria Graciela} and Domingo Palmero and Carlos P{\'e}rez-Guzm{\'a}n and Vargas, {Mario H.} and Lia D'Ambrosio and Antonio Spanevello and Melissa Bauer and Chan, {Edward D.} and Schaaf, {H. Simon} and Salmaan Keshavjee and Holtz, {Timothy H.} and Dick Menzies and S. Ahuja and D. Ashkin and M. Avendano and R. Banerjee and Bayona, {J. N.} and Becerra, {M. C.} and A. Benedetti and M. Burgos and Chiang, {C. Y.} and H. Cox and Dung, {N. H.} and D. Enarson and K. Flanagan and J. Flood and L. Garcia-Garcia and Granich, {R. M.} and Iseman, {M. D.} and Jarlsberg, {L. G.} and Kim, {H. R.} and Koh, {W. J.} and J. Lancaster and C. Lange and {De Lange}, {W. C.M.} and V. Leimane and Leung, {C. C.} and J. Li and Mishustin, {S. P.} and Mitnick, {C. D.} and M. Narita and P. O'Riordan and M. Pai and Park, {S. K.}",

year = "2013",

month = jul,

day = "1",

doi = "10.1183/09031936.00136312",

language = "English (US)",

volume = "42",

pages = "169--179",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "1",

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TY - JOUR

T1 - Drug resistance beyond extensively drugresistant tuberculosis

T2 - Individual patient data meta-analysis

AU - Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

AU - Migliori, Giovanni Battista

AU - Sotgiu, Giovanni

AU - Gandhi, Neel R.

AU - Falzon, Dennis

AU - DeRiemer, Kathryn

AU - Centis, Rosella

AU - Hollm-Delgado, Maria Graciela

AU - Palmero, Domingo

AU - Pérez-Guzmán, Carlos

AU - Vargas, Mario H.

AU - D'Ambrosio, Lia

AU - Spanevello, Antonio

AU - Bauer, Melissa

AU - Chan, Edward D.

AU - Schaaf, H. Simon

AU - Keshavjee, Salmaan

AU - Holtz, Timothy H.

AU - Menzies, Dick

AU - Ahuja, S.

AU - Ashkin, D.

AU - Avendano, M.

AU - Banerjee, R.

AU - Bayona, J. N.

AU - Becerra, M. C.

AU - Benedetti, A.

AU - Burgos, M.

AU - Chiang, C. Y.

AU - Cox, H.

AU - Dung, N. H.

AU - Enarson, D.

AU - Flanagan, K.

AU - Flood, J.

AU - Garcia-Garcia, L.

AU - Granich, R. M.

AU - Iseman, M. D.

AU - Jarlsberg, L. G.

AU - Kim, H. R.

AU - Koh, W. J.

AU - Lancaster, J.

AU - Lange, C.

AU - De Lange, W. C.M.

AU - Leimane, V.

AU - Leung, C. C.

AU - Li, J.

AU - Mishustin, S. P.

AU - Mitnick, C. D.

AU - Narita, M.

AU - O'Riordan, P.

AU - Pai, M.

AU - Park, S. K.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

AB - The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cycloserine/ terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95%CI 0.2- 0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.

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DO - 10.1183/09031936.00136312

M3 - Article

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AN - SCOPUS:84880158505

SN - 0903-1936

VL - 42

SP - 169

EP - 179

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 1

ER -

Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

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